This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Laser immunotherapy is a novel modality, which utilizes the direct tumor destruction by selective phototherapies and the indirect, long-term effect of immunological stimulation, for the treatment of metastatic tumors. The combination of photoirradiation and in situ applications of immunoadjuvants has induced tumor-specific immunity in previous animals studies. The overall objective of this project is to optimize the modality and to understand its biological mechanism. Methods: Magnetic Resonance Imaging (MRI) technique was used to monitor selective laser thermal treatment of phantom gel, chicken tissue and mouse tumors in order to test the hypothesis of temperature control in laser treatment. Two novel immunoadjuvants, glycated chitosan (GC) and imiquimod (IMQ), were intralesionally injected to mice bearing B16 melanoma and the responses of the animals were studied. To further study the effect of the combination of laser of immunoadjuvant, photodynamic therapy (PDT) and glycated chitosan were used in the treatment of EMT6 mammary tumors and Line 1 lung tumors in mice. Results: The MRI images of the target tissue and animal tumors during laser irradiation showed clear tissue structure changes and temperature distribution. Animal experiments showed that when the GC and IMQ were used together, the tumor growth was significantly slowed. In the treatment of EMT6 mammary sarcoma in mice, GC of 0.5% and 1.5% concentrations increased the cure rates of Photofrin-based PDT treatment from 38% to 63% and 75%, respectively. In the treatment of Line 1 lung adenocarcinoma in mice, a 1.67% GC solution enabled a non-curative mTHPC-based PDT to cure 37% of the tumor bearing mice. Conclusion: Following the current studies, it is expected that the control of tissue temperature during laser irradiation can be achieved, making the optimization of thermal treatment possible. Future study will also demonstrate the enhancement of immune responses in tumor treatment using the combination of laser and immunoadjuvants. Ultimately, this method could be applied clinically for the patients with metastatic tumors.